81 articles - From Friday Dec 30 2022 to Friday Jan 06 2023
Guidelines and related publications, position statements, white papers, technical reviews, consensus statements, etc…
| Am J Hematol |
Assessment of renal outcome following therapy in monoclonal immunoglobulin deposition disease: Emphasizing the need for a consensus approach. With a median follow-up of 110 months, the median overall survival was 136 months (95% CI: 79-NR) and median renal survival had not been reached. Prospective studies using uniform renal response criteria are needed to optimize the management of MIDD. |
Clinico-genetic and prognostic analyses of 716 patients with primary myelodysplastic syndrome and myelodysplastic syndrome/acute myeloid leukemia based on the 2022 International Consensus Classification. Patients with mutated TP53 were associated with dismal outcomes, irrespective of the blast percentage. In conclusion, this study showed that the ICC facilitates efficient segregation and risk-stratification of MDS which can help guide the treatment choice of patients with the disease. |
meta-analyses and systematic reviews
| Blood Cancer J |
The prevalence and outcomes of frail older adults in clinical trials in multiple myeloma: A systematic review. Most studies demonstrated a consistent benefit of MM interventions among the frail and non-frail populations, however in general, frail patients had worse outcomes compared to the fit. Although frailty is increasingly being incorporated in MM clinical trials, due to the variation in both the definition and categorization of frailty, there remains heterogeneity in the prevalence of frailty and its potential associated impact on outcomes. |
| Thromb Haemost |
Venous Thromboembolism Associated with Assisted Reproductive Technology: A Systematic Review and Meta-analysis. Risk factors of VTE associated with ART were in vitro fertilization procedure (RR, odds ratio [OR], and hazard ratio varying from 1.77, 95% CI: 1.41-2.23 to 4.99, 95% CI: 1.24-20.05), hyperhomocysteinemia (OR: 15.2; 95% CI: 2.0-115.0), polycystic ovarian syndrome (PCOS) (RR: 4.8; 95% CI: 1.7-13.4), successful ART leading to pregnancy (OR: 13.94; 95% CI: 1.41-137.45). Further large prospective studies on risk factors of VTE in women undergoing ART are needed in order to optimize thromboprophylaxis in this context. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification and management. Such advances are welcome, but the increased options also lead to many controversies concerning the optimal selection of the timing and combinatorial use of the new drugs and how best to leverage our burgeoning ability to measure a small number of potentially malignant myeloid cells. In this context, we will present our approach for AML management noting current limitations and potential future directions. |
Atypical chronic myeloid leukemia and myelodysplastic/myeloproliferative neoplasm, not otherwise specified: 2023 update on diagnosis, risk stratification, and management. DNMT inhibitors have been used in both entities with suboptimal response rates. Allogeneic stem cell transplant remains the only curative strategy but is associated with high morbidity and mortality. |
Clinical characteristics and outcome of 318 families with familial monoclonal gammopathy: A multicenter Intergroupe Francophone du Myélome study. The median overall survival of the 148 familial MM cases was longer than that of matched sporadic cases, with projected values of 7.6 and 16.1 years in patients older and younger than 65 years, respectively. These data suggest that familial cases of monoclonal gammopathy are similar to sporadic cases in terms of clinical presentation and carry a better prognosis. |
Clinical outcomes and prognostic risk factors of Langerhans cell histiocytosis in children: results from the BCH-LCH 2014 protocol study. Multivariate analysis revealed that early treatment response, the involvement of RO, skin, and oral mucosa, as well as laboratory parameters, including CRP and |
Frontline combination of ponatinib and hyper-CVAD in Philadelphia chromosome-positive acute lymphoblastic leukemia: 80-months follow-up results. Two ponatinib-related deaths from myocardial infarction (3%; at months 2.6 and 4.3, respectively; both in CR) in the first 37 patients treated led to the ponatinib dose-modifications mentioned earlier, with no further ponatinib-related deaths observed. The long-term results of ponatinib and hyper-CVAD continue to demonstrate excellent outcome results and acceptable safety data, indicating that this strategy is another standard of care approach in frontline Ph-positive ALL. |
Hematopoietic stem cell donor vaccination with CMV Triplex augments frequencies of functional and durable CMV-specific T cells in the recipient: a novel strategy to limit antiviral prophylaxis. CMV viremia requiring antivirals developed in three recipients (18%). In summary, this novel approach represents a promising strategy applicable to different HCT settings for limiting the use of antiviral prophylaxis, which can impair and delay CMV-specific immunity, leading to CMV reactivation requiring treatment |
Idarubicin plus BuCy versus BuCy conditioning regimens for intermediate-risk acute myeloid leukemia in first complete remission undergoing auto-HSCT: An open-label, multicenter, randomized phase 3 trial. This trial is registered with ClinicalTrials. gov, NCT02671708, and is complete. |
N-terminal pro-brain natriuretic peptide is a prognostic marker for response to intensive chemotherapy, early death, and overall survival in acute myeloid leukemia. In multivariate analysis, NT-proBNP, age, and ELN-2009 remained independent prognostic variables for OS (p < .01). Together, NT-proBNP is an independent prognostic factor indicating the risk of induction failure, early death, and reduced OS in patients with AML. |
Outcome of limited-stage peripheral T-Cell lymphoma after CHOP(-like) therapy: A population based study of 239 patients from the Nordic lymphoma epidemiology group. In the present study of limited-stage nodal PTCL, survival after curative intent chemotherapy +/- radiotherapy was inferior to that of limited-stage diffuse large B-cell lymphoma, but a subgroup of young patients without B-symptoms had very good outcomes. Treatment outcomes after 3-4 cycles versus 6-8 cycles of CHOP(-like) therapy were comparable. |
Outcomes of patients with limited-stage plasmablastic lymphoma: A multi-institutional retrospective study. Multivariate regression analysis (MRA) demonstrated improved PFS for patients receiving EPOCH based frontline therapy versus CHOP (HR: 0.23; p = 0.029). Frontline chemotherapy followed by radiation consolidation versus chemotherapy alone appeared to be associated with improved relapse and survival outcomes but did not show statistical significance in MRA. |
Overall and complication-free survival in a large cohort of patients with ß-thalassemia major followed over 50 years. A progressive decrease in the median age of BMT was observed in younger birth cohorts (p 1000 ng/mL (HR: 15.5, 95%CI: 3.52-68.2, p < 0.001), male sex (HR: 2.75, 95%CI: 0.89-8.45, p = 0.078), and splenectomy (HR: 6.97, 95%CI: 0.90-54.0, p < 0.063). Survival in patients with ß-thalassemia major continues to improve with adequate access to care, best practice sharing, continued research, and collaboration between centers. |
Pregnancy outcomes in women with sickle cell disease in California. Despite adjusting for sociodemographic factors, Black women with SCD still experienced significantly worse pregnancy outcomes than those without SCD. We need additional studies to determine if early introduction to reproductive health education, continuation of SCD-modifying therapies during pregnancy, and increasing access to multidisciplinary perinatal care can reduce morbidity in pregnant women with SCD. |
Survival trends in young patients with Waldenström macroglobulinemia: Over five decades of experience. Despite a protracted disease course, nearly al young patients succumb to their disease. In contrast to the improved survival of the elderly patient population, the evolving treatment strategies in WM have not impacted the outcome of young patients; however, the impact of Bruton tyrosine kinase inhibitors on this unique patient population remains to be determined. |
Targeting MCL-1 and BCL-2 with polatuzumab vedotin and venetoclax overcomes treatment resistance in R/R NHL: Results from preclinical models and a Phase Ib study. This targeted MCL-1 antagonism, when combined with venetoclax and the anti-CD20 antibodies obinutuzumab or rituximab, results in tumor regressions in preclinical NHL models, which are sustained even off-treatment. In a Phase Ib clinical trial (NCT02611323) of heavily pre-treated patients with relapsed or refractory NHL, 25/33 (76%) patients with follicular lymphoma and 5/17 (29%) patients with diffuse large B-cell lymphoma achieved complete or partial responses with an acceptable safety profile when treated with the recommended Phase II dose of polatuzumab vedotin in combination with venetoclax and an anti-CD20 antibody. |
The Composite Immune Risk Score predicts overall survival after allogeneic hematopoietic stem cell transplantation: A retrospective analysis of 1838 cases. I., 1.28-2.55; p = .00085). In conclusion, the Composite Immune Risk Score is easy to compute and could identify the high-risk patients of allogeneic HSCT who require targeted effort for prevention and control of infection. |
Thrombosis in multiple myeloma: Risk estimation by induction regimen and association with overall survival. The association of TE with reduced survival demonstrated in univariate analysis (HR = 2.2, 95% CI = 1.6-3.3) was maintained in the multivariable analysis adjusted for high-risk interphase fluorescence in situ hybridization (FISH), sex, age, receipt of an upfront transplant, the response at induction, and the International Staging System (ISS) (HR = 2.61, CI = 1.74-3.9). We conclude that TE is an important aspect of MM management, and effective management is especially relevant in the novel treatment era. |
Waldenström macroglobulinemia: 2023 update on diagnosis, risk stratification, and management. Management of refractory disease Bortezomib, cyclophosphamide, fludarabine, thalidomide, everolimus, Bruton Tyrosine Kinase inhibitors, carfilzomib, lenalidomide, bendamustine, and venetoclax have al been shown to have activity in relapsed WM. Given WM's natural history, the reduction of therapy toxicity is an important part of treatment selection. |
| Blood |
Central Nervous System Status is Prognostic in T-Cell Acute Lymphoblastic Leukemia: A Children's Oncology Group Report. Unlike with B-ALL, CNS-2 status in T-ALL does not impact outcome in the context of aBFM therapy, without additional intrathecal therapy, with or without CRT. Although nelarabine improved outcomes for those with CNS-3 status, novel approaches are needed for further improvements. |
DNA polymerase theta protects leukemia cells from metabolic-induced DNA damage. Moreover, OTK inhibitor or DPC-inducing drug etoposide enhanced anti-leukemia effect of POLq inhibitor (POLqi) in vitro and in vivo. In conclusion, we demonstrated that POLq plays an essential role in protecting leukemia cells from metabolically induced toxic DNA lesions triggered by formaldehyde and that it can be targeted to achieve therapeutic effect. |
High-Dose Melphalan Treatment Significantly Increases Mutational Burden at Relapse in Multiple Myeloma. This similarity could be due to HDM relapse samples having significantly more neoantigens. Overall, our study identifies increased genomic changes associated with HDM and provides rationale to further understand clonal complexity. |
INPP5K controls the dynamic structure and signaling of wild type and mutated, leukemia-associated IL7 receptors. Similar alterations following reduced INPP5K expression also impacted mutated, constitutively activated IL7Ra chains that trigger leukemia development, leading to reduced cell proliferation. Altogether, our results indicate that the lipid 5-phosphatase INPP5K hydrolyses plasma membrane PtdIns(4,5)P2, allowing the requisite conformational changes of the IL7Ra chain for optimal signaling. |
MYB insufficiency disrupts proteostasis in hematopoietic stem cells leading to age-related neoplasia. Linking to previous studies showing the importance of proteostasis in HSC maintenance, we observed altered proteosomal activity in young Myb-insufficient mice as well as elevated proliferation indicators, followed later by elevated ribosome activity. We propose that these alterations combine to cause an imbalance in proteostasis, potentially creating a cellular milieu favoring disease initiation. |
Removal of the vicinal disulfide enhances the platelet capturing function of Von Willebrand Factor. Differential scanning calorimetry and Hydrogen-Deuterium exchange mass spectrometry demonstrate that reduction of the vicinal disulfide destabilizes the A2 domain which consequently disrupts interactions between the A1, A2, and A3 domains and enhances the conformational dynamics of A1-domain secondary structures known to regulate the strength of platelet adhesion to VWF. This study clarifies that the reduced state of the A2 vicinal disulfide is not inhibitory, but rather slightly activating. |
Type 2B von Willebrand disease mutations differentially perturb autoinhibition of the A1 domain. Lastly, examination of the mechanical stability of each variant revealed variable AIM unfolding. Together, these studies illustrate that the heterogeneity among type 2B VWD mutations is evident in AIM-A1 fragments. |
| Blood Adv |
A comprehensive landscape of transcription profiles and data resource for human leukemia. g., the HOXA9 module in AML and the NOTCH1 module in T-ALL. In summary, the developed LeukemiaDB provides valuable insights into oncogenesis and progression of leukemia and, to the best of our knowledge, is the most comprehensive transcriptome resource of human leukemia available to the research community. |
A novel mouse whole blood thrombin generation assay sensitive to FXI- and FIX-mediated amplification of coagulation. In conclusion, we have developed a novel mouse WB-TG assay with enhanced sensitivity to FXI- and FIX-dependent amplification of coagulation compared to an established plasma-TG assay. The enhanced sensitivity of WB-TG to FXI and FIX dependent amplification of coagulation suggests an important role of blood cells in this process. |
Dasatinib-induced spleen contraction leads to transient lymphocytosis. Finally, we uncovered a decrease in spleen size of CML patients who showed lymphocytosis immediately following dasatinib treatment, and this reduction was proportional to the magnitude of lymphocytosis and dasatinib plasma levels. In sum, our work provides evidence that dasatinib-induced lymphocytosis is a consequence of drug-induced contractility of splenic stromal cells. |
Impact of GVHD prophylaxis on CMV reactivation and disease after HLA-matched peripheral blood stem cell transplantation. In contrast, MMF was associated with higher overall CMV viral burden in the 1-year posttransplant. While different mechanisms of immunosuppressive agents may impact CMV reactivation risk, effective prevention of GVHD may reduce corticosteroid exposure and mitigate infection risk over time. |
Posttransplantation Cyclophosphamide Expands Functional Myeloid-Derived Suppressor Cells and Indirectly Influences Tregs. The clinical implications of these findings, including the potential impact of expanded MDSCs after PTCy on engraftment and cytokine release syndrome, remain to be elucidated. Moreover, the indirect effect that PTCy has on Tregs, which in turn play a necessary role in GVHD prevention by initially transplanted or subsequently infused T cells, requires further investigation. |
Proteome alterations in erythrocytes with PIEZO1 gain-of-function mutations. This finding provides also an explanation of the pathogenetic mechanism underlying the increased thrombotic rate observed in these patients. Finally, the newly identified proteins, involved in the intracellular signaling pathways altered by PIEZO1 mutations, could be used in the future as potential druggable targets in DHS. |
| Blood Cancer J |
Determinants of survival and retrospective comparisons of 183 clinical trial patients with myelofibrosis treated with momelotinib, ruxolitinib, fedratinib or BMS- 911543 JAK2 inhibitor. In addition, spleen (p < 0.01) and anemia (p = 0.01) responses were independently associated with improved short-term survival while long-term survival was secured only by ASCT (5/10-year survival rate 91%/45% vs 47%/19% in non-transplanted patients; p < 0.01). The current retrospective study suggests the value of specific pre-treatment variables in identifying long-lived MF patients receiving JAKi and also confirms recent observations on the favorable impact of treatment response on short-term and of ASCT on long-term survival. |
One-year breakthrough SARS-CoV-2 infection and correlates of protection in fully vaccinated hematological patients. Our study describes the incidence of and risk factors for COVID-19 breakthrough infections during the initial vaccination and booster doses in the 2021 to mid-2022 period. The level of antibody titers at any time after 2-dose vaccination is strongly linked with protection against both breakthrough infection and severe disease, even with the Omicron SARS-CoV-2 variant. |
Poor prognostic implications of myelodysplasia-related mutations in both older and younger patients with de novo AML. In summary, AML patients with MDS-R mutations have significantly poorer outcomes regardless of age. More intensive treatment, such as allo-HSCT and/or novel therapies, is warranted for AML patients with MDS-R mutations. |
Real-world use of blinatumomab in adult patients with B-cell acute lymphoblastic leukemia in clinical practice: results from the NEUF study. Median (95% confidence interval) OS was 12.2 (7.3-24.2) months in the R/R Ph- subgroup and 16.3 (5.3-not estimated) months in the R/R Ph+ subgroup. This large, real-world data set of adults with B-cell ALL treated with blinatumomab confirms efficacy outcomes from published studies. |
| Haematologica |
A novel next-generation sequencing capture-based strategy to report somatic hypermutation status using genomic regions downstream to immunoglobulin rearrangements. Overall, 84/95 (88.4%) CLL cases with conventional SHM data showed concordant SHM status, increasing to 91.6% when excluding borderline cases. Additionally, IGHJ-E mutation analysis in a wide range of pre- and post-germinal centre LPD showed significant correlation with differentiation and lineage status, suggesting that IGHJ-E analysis is a promising surrogate marker enabling SHM to be reported using NGS-capture strategies and whole genome sequencing. |
| J Hematol Oncol |
miRNome profiling of lung cancer metastases revealed a key role for miRNA-PD-L1 axis in the modulation of chemotherapy response. Mechanistically, we discovered a miR-455-5p/PD-L1 regulatory axis which drives chemotherapy resistance, hallmarks metastases with active IFN- |
| Leukemia |
High caspase 3 and vulnerability to dual BCL2 family inhibition define ETO2::GLIS2 pediatric leukemia. We further show that combined inhibition of BCL2 and MCL1 is mandatory to abrogate disease progression using in vivo patient-derived xenograft models. These data reveal that a transcriptional consequence of ETO2::GLIS2 expression includes a positive regulation of the pro-apoptotic CASP3 and associates with a vulnerability to combined targeting of two BCL2 family members providing a novel therapeutic perspective for this aggressive pediatric AML subgroup. |
Real-life disease monitoring in follicular lymphoma patients using liquid biopsy ultra-deep sequencing and PET/CT. LiqBio-MRD and PET/CT combined identified the patients that progressed in less than two years with 88% sensitivity and 100% specificity. Our results demonstrate that LiqBio-MRD is a robust and non-invasive approach, complementary to metabolic imaging, for identifying FL patients at high risk of failure during the treatment and should be considered in future response-adapted clinical trials. |
| Thromb Haemost |
Longitudinal in vivo monitoring of atheroprogression in hypercholesterolemic mice using photoacoustic imaging. s- The present study shows an innovative approach to assess arterial inflammation in a non-invasive fashion, applicable to longitudinal analyses of changes of atherosclerotic lesion composition. Such approach could prove important in the preclinical testing of therapeutic interventions in mice carrying pre-established lesions. |
Platelet P2Y12 Inhibitor Monotherapy after Percutaneous Coronary Intervention: An Emerging Option for Antiplatelet Therapy De-escalation. This survey reviews the evidence on P2Y12 blocker monotherapy. Some clinical guidance will be provided on when and in whom P2Y12 inhibitor monotherapy may be applied after DAPT cessation following PCI. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Am J Hematol |
| Blood |
| Blood Cancer J |
Lymphoid clonal hematopoiesis: implications for malignancy, immunity, and treatment. Unlike myeloid clonal hematopoiesis (M-CH), L-CH has the potential to originate at both stem cells and partially or fully differentiated progeny stages of maturation. In this review, we explore the definition of L-CH in the context of lymphocyte maturation and lymphoid malignancy precursor disorders, the evidence for L-CH in late-onset autoimmunity and immunodeficiency, and the development of therapy-related L-CH following chemotherapy or hematopoietic stem cell transplantation. |
misc publications eg case reports, tools of the trade, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Thromb Haemost |
Letters to the editors and authors’ replies
| Am J Hematol |
| Ann Oncol |
| Blood Cancer J |
| Haematologica |
| J Hematol Oncol |
FTL004, an anti-CD38 mAb with negligible RBC binding and enhanced pro-apoptotic activity, is a novel candidate for treatments of multiple myeloma and non-Hodgkin lymphoma. Cryo-electron microscopy structure resolved two epitope centers of FTL004 on CD38: one of which was unique while the other partly overlapped with that of isatuximab. Taken together, FTL004 distinguishes it from other CD38 targeting mAbs and represents a potential candidate for the treatment of MM and non-Hodgkin lymphoma. |
The development of a cSMART-based integrated model for hepatocellular carcinoma diagnosis. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for al stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs. |